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This press release contains:

· Summaries of newsworthy papers:

Biotechnology: Stopping the pumps in chemotherapy-resistant tumours

Geoscience: Mississippi drowning

Genetics: Genetic variants associated with kidney stones

Chemical Biology: Metabolism in motion

Nature: Solid-state quantum circuits

Immunology: Mystery solved for immunoglobulin D role

Geoscience: Future forest changes

Chemical Biology: Efficiently moving through chemical space

Geoscience: Tropical rain shift 600 years ago

And finally…Immunology: Uncovering allergy bias

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

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A novel type of artificial drug delivery system that blocks cancer cells’ ability to expel chemotherapy and thereby acquire drug resistance is published online this week in Nature Biotechnology. In mice, this approach successfully inhibits the growth of drug-resistant colon, breast and uterine tumours and substantially extends life expectancy.

Himanshu Brahmbhatt and colleagues’ technique relies on minicells – empty, lifeless bacteria without genetic material – which can be filled with different types of drug. Mice were sequentially given two sets of minicells – the first filled with small RNA molecules to block production of the pumps that confer drug-resistance, and the second one loaded with toxic chemotherapy drugs to kill the tumour cells with disabled pumps.

Since the drugs are not released into general circulation, they can kill cancer cells at much lower dosage than normally required, thus avoiding undesirable side effects.

Sediments deposited in the Mississippi delta cannot keep up with regional sea-level rise, suggests a study published online in Nature Geoscience. The researchers propose that the imbalance makes the submergence of the delta inevitable.

Michael Blum and Harry Roberts examined rates of sediment deposition in the Mississippi delta over the past 12,000 years and found that the Mississippi carried substantially more sediments before dam building started. They estimated that 18–24 billion tons of sediment would be required by 2100 to sustain the existing surface area of the Mississippi delta as sea levels rise. This exceeds current supply in the Mississippi river.

The researchers suggest that without an increase in sediment load, 10,000 to 13,500 square kilometres of deltaic land will be lost by 2100.

Common genetic variants are associated with an increased risk of kidney stone disease, according to a study published online in this week’s Nature Genetics.

Kidney stone disease is a common disorder in the West and although it has a clear heritable component, common genetic risk factors had not yet been discovered.

Gudmar Thorleifsson and colleagues examined the genomes of 46,283 individuals and found that common variants within the CLDN14 gene are significantly associated with kidney stone disease. Individuals with certain CLDN14 variants can have a slightly increased risk of developing kidney stone disease compared to individuals who do not have the risk-associated variants.

The CLDN14 gene encodes a protein that likely regulates important cellular functions in the kidney, although further research is needed to determine how this protein might affect kidney stone formation.

A quantitative and comprehensive investigation of enzyme reactions within cells is published online in this week’s Nature Chemical Biology. The findings provide the groundwork to ask more specific questions about how cells interact with their natural environment and how they control their own metabolism.

Cellular metabolism includes the creation and consumption of small molecules, or metabolites, that are used in creating proteins, the cell membrane, and in many other biological processes. The reactions for these biological processes are facilitated by enzymes.

Metabolites are often studied by determining relative concentrations of various molecules – the amount of one compound in comparison to another. Joshua Rabinowitz and colleagues used several metabolomic analysis tools to determine the absolute concentration, or the specific amount of compounds in cells independent of any other molecules. By comparing these concentrations to a database of known enzyme parameters, the scientists were able to tell which of the cell’s molecules are constantly being used in reactions, and which are likely being used to respond to other factors such as whether the cell is actively growing, or under attack.

An electrically controlled, solid-state quantum processor has been put through its paces by executing two quantum algorithms. The results are revealed in this week's Nature.

The superconducting processor, reported by Leonardo DiCarlo and colleagues, represents an important step in quantum computing with integrated circuits. Quantum processors based on a few quantum bits have been demonstrated before using nuclear magnetic resonance, cold ion traps and optical systems, but making a solid-state processor proved difficult.

The current prototype contains just two quantum bits, but holds promise for a fully scalable technology.

The function of the antibody called immunoglobulin D has puzzled immunologists for years. A study in Nature Immunology reports that immunoglobulin D helps combat upper respiratory infections.

Andrea Cerutti and colleagues show antibody-producing cells located in tonsils and upper airway tissues release immunoglobulin D (IgD). IgD then recognizes bacteria and other disease-causing microbes. IgD-bound bacteria trigger immune cells known as basophils to release fever-inducing agents and a variety of antimicrobial substances to rid the infectious agent.

This work therefore places IgD antibodies as a foot soldier in the immune arsenal against respiratory infections.

Even if climate change is halted, ecosystems will probably continue to change for a long time, according to a study published online this week in Nature Geoscience. The work suggests that our commitment to future changes in ecosystems through past changes in climate needs to be taken into account when determining levels of ‘dangerous climate change’.

Chris Jones and colleagues analysed simulations with a coupled climate–vegetation model to investigate long-term effects of climatic changes on terrestrial ecosystems. They ran a number of climate-change simulations but stabilized the climate in each run at a different level of atmospheric greenhouse gases. In their simulations, forest coverage continues to change significantly for decades after the climatic boundary conditions have been held constant.

The authors conclude that substantial reduction in tropical forest coverage and spreading of high-latitude forests could be inevitable before the ecosystem changes are observed.

A new user-friendly software tool for navigating chemical space and an application of this tool in identifying drug leads more efficiently are reported in two papers online this week in Nature Chemical Biology.

Chemical space – all possible chemical molecules – is enormous and it can be difficult to easily understand how different chemicals relate to one another. Better understanding the connection between related chemical structures and their associated biological activity would help in efficiently identifying new drug leads.

Herbert Waldmann and colleagues developed a computer software program that creates trees in which a ‘branch’ starts from a complicated chemical structure and is gradually broken down to its simpler chemical components. By using biological activity data – for instance which chemicals in a large chemical library inhibit a particular enzyme – to guide the creation of these chemical trees, the authors are able to identify new inhibitors, which have significantly different chemical structures from the known inhibitors for particular drug targets.

During the Little Ice Age, the Pacific section of the circumglobal tropical rainbelt was up to 500 km south of its present position. Published online in this week’s Nature Geoscience, these results indicate a very sensitive response of tropical rainfall patterns — which many people in Africa, Asia and South America rely on for subsistence agriculture — to small changes in Earth’s radiation budget.

Julian Sachs and colleagues use microbiological, molecular and isotopic analyses of lake sediments from three islands in the eastern, central and western equatorial Pacific Ocean, respectively, to determine wet and dry periods on each island. The periods of humidity they identify in the three locations suggest that the intertropical convergence zone — which marks the position of the most vigorous rainfall events — were substantially further south than today between about ad 1400 and 1850. At this time, European temperatures were relatively cool, possibly owing to low solar radiation.

A gene that helps explain why some individuals are more likely to develop allergies is reported online in this week’s Nature Immunology. These findings increase our understanding of how immune cells that impact infectious, autoimmune, and allergic disease susceptibility are regulated.

‘Type 2’ immunity is necessary for resistance to parasites but can also lead to allergic reactions. A team led by Mark Bix and Masato Kubo trace the genetic bias underlying development of ‘type 2’ immunity to expression of the gene Mina.

Mina encodes a protein that blocks early expression of interleukin 4 (IL-4), a key molecule responsible for inducing allergic-like immune responses. Immune cells from allergic-prone mice express less Mina protein and consequently express IL-4 more readily than those from strains lacking this bias.

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Items from other Nature journals to be published online at the same time and with the same embargo:

The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

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